Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-24T10:44:31.305Z Has data issue: false hasContentIssue false

23 - Clomiphene Citrate for Ovulation Induction

from PART II - INFERTILITY EVALUATION AND TREATMENT

Published online by Cambridge University Press:  04 August 2010

By
Richard Palmer Dickey
Edited by
Botros R. M. B. Rizk ,
Juan A. Garcia-Velasco ,
Hassan N. Sallam  and
Antonis Makrigiannakis
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

Clomiphene revolutionized the management of infertility in 1967 when it was approved for treatment of anovulation due to polycystic ovaries (PCO). The clinical introduction of clomiphene followed six years of research (Greenblatt et al., 1961; Tyler et al., 1962; Vorys et al., 1964; Dickey et al., 1965; Kistner, 1966) cumulating in a report of results in 3,220 patients and 1,032 conceptions (Table 23.1) (Macgregor et al., 1967; Macgregor et al., 1968). Today, clomiphene remains the first-line treatment for WHO Group II anovulation in which ovarian activity can be demonstrated by withdrawal bleeding from progesterone. In addition to treatment of anovulation, clomiphene is now also used alone and in combination with human menopausal gonadotropin (HMG) and follicle-stimulating hormone (FSH) to increase the number of preovulatory follicles in patients with unexplained infertility (Melis et al., 1987; Deaton et al., 1990; Glazener et al., 1990), in patients requiring husband or donor intrauterine insemination (IUI) (Shalev et al., 1989; Dickey et al., 1992), and to increase progesterone in patients with luteal insufficiency (Hammond and Taubert, 1982; Fukuma et al., 1983; Dickey, 1984; Guzick and Zeleznik, 1990). The advantages of clomiphene over gonadotrophin for ovulation induction include low incidence of multiple pregnancies, low cost, ease of treatment, absence of need for daily cycle monitoring, and low incidence of ovarian hyperstimulation syndrome (OHSS) (Rizk, 2006, 2008; Rizk and Dickey 2008).

PHARMACOKINETICS AND PHARMACODYNAMICS

The pharmacokinetics and pharmacodynamics of clomiphene explain its characteristic actions. Clomiphene, chemical name 1-[p(β-diethylaminoethoxy)phenyl]-1,2-diphenylchloroethylene (Holtkamp et al., 1960), is related to other trianyl ethylene compounds chlorotrianisene, triparanol (a cholesterol inhibitor), and tamoxifen, a class of drugs called selective estrogen receptor modulators (Figure 23.1) and is distantly related to the nonsteroidal estrogen diethylstilbestrol.

Keywords

cervical mucusclqmiphene citrateintrauterine inseminationovulation inductionprogesteronepolycystic ovaries
Type
Chapter
Information
Infertility and Assisted Reproduction , pp. 202 - 219
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

Acharya, U, Irvine, DS, Hamilton, MP, Templeton, AA (1993) The effect of three anti-oestrogen drugs on cervical mucus quality and in-vitro sperm-cervical mucus interaction in ovulatory women. Hum Reprod 8:437–41.CrossRefGoogle ScholarPubMed
Adams, R, Mishell, DR, Israel, R (1972) Treatment of refractory anovulation with increased and prolonged duration of cyclic clomiphene citrate. Obstet Gynecol 39:562–6.Google ScholarPubMed
Adashi, EY (1996) Ovulation induction: clomiphene citrate. In Adashi, EY, Rock, JA, Rosenwaks, , eds. Reproductive Endocrinology, Surgery, and Technecology. Chapter 59. Lippincott-Raven Publishers, Philadelipha, pp. 1181–206.Google Scholar
Adashi, EY, Rock, JA, Sapp, KC, et al. (1979) Gestational outcome of clomiphene-related conceptions. Fertil Steril 31:620–6.CrossRefGoogle ScholarPubMed
Asch, RH, Greenblatt, RB (1976) Update on the safety and efficacy of clomiphene citrate as a therapeutic agent. J Reprod Med 17:175–80.Google ScholarPubMed
Bergqvist, C, Nillius, SJ, Wide, L (1983) Human gonadotropin therapy. II. Serum estradiol and progesterone patterns during nonconceptual cycles. Fertil Steril 39:766–71.Google Scholar
Boue, Boue (1973) Increased frequency of chromosomal anomalies in abortions after induced ovulation. Lancet 1:679–80.CrossRefGoogle ScholarPubMed
Charles, D, Klein, T, Lunn, SF, Loraine, JA (1969) Clinical and endocrinological studies with isomeric components of clomiphene citrate. J Obstet Gynaecol Br Commonw 76:1100–10.CrossRefGoogle ScholarPubMed
Chaukin, W (1982) The rise in ectopic pregnancy exploration of possible reasons. Int J Gynecol Obstet 20:341–50.CrossRefGoogle Scholar
Clark, JH, Markaverich, BM (1988) Actions of ovarian steroid hormones. In Knobil, E, Neill, J et al., eds. The Physiology of Reproduction. Raven Press, New York, pp. 675–723.Google Scholar
Connaughton, JF, Garcia, C-R, Wallach, EE (1974) Induction with cisclomiphene and a placebo. Obstet Gynaceol 43:697–701.Google ScholarPubMed
Corson, SL, Batzer, DR, Otis, C, Corson, J (1983) Clomiphene citrate: nuances of clinical application. Clin Reprod Fertil 2:1–17.Google ScholarPubMed
Corson, SL, Batzer, FR, Alexander, NG, et al. (1984) Sex selection by sperm separation and insemination. Fertil Steril 42:756–60.CrossRefGoogle ScholarPubMed
Daly, DC, Walters, CA, Soto-Albors, CE, et al. (1984) A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Fertil Steril 41:844–8.CrossRefGoogle ScholarPubMed
Deaton, JL, Gibson, M, Blackmer, KM, et al. (1990) A randomized controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertil Steril 54:1083–8.CrossRefGoogle ScholarPubMed
Dickey, RP (1984) Evaluation and management of threatened and habitual first trimester abortion. In Osofsky, H., ed. Advances in Clinical Obstetricts and Gynecology, Vol. 2, Chapter 2. Yearbook Medical Publishers, Chicago, pp. 329–88.Google Scholar
Dickey RP (2003) Superovulation/IUI rather than IVF should be the primary management for patients with unexplained infertility. Presented at 2003 ASRM Annual Meeting, San Antonio, TX, Oct. 2003.
Dickey, RP (2006) Managing Oral Contraceptive Pill Patients, 13th edn. EMIS Dallas, Texas.Google Scholar
Dickey, RP (2008) Ultrasonography of the endometriosis. In Rizk, B. (ed.), Ultrasonography in Reproductive Medicine and Infertility. Cambridge: United Kingdom, Cambridge University Press, (in press).Google Scholar
Dickey, RP, Hower, JF (1995) Effect of ovulation induction on uterine blood flow and oestradiol and progesterone concentrations in early pregnancy. Hum Reprod 10:2875–9.CrossRefGoogle ScholarPubMed
Dickey, RP, Matis, R, Olar, TT, et al. (1989) The occurrence of ectopic pregnancy with and without clomiphene citrate use in assisted and non-assisted reproductive technology. J In Vitro Fertil Embryo Transfer 6:294–7.CrossRefGoogle Scholar
Dickey, RP, Olar, TT, Curole, DN, et al. (1990) The probability of multiple births when multiple gestational sacs or viable embryos are diagnosed at first trimester ultrasound. Hum Reprod 5:880–2.CrossRefGoogle ScholarPubMed
Dickey, RP, Olar, TT, Taylor, SN, et al. (1991) Relationship of follicle number, serum estradiol, and other factors to birth rate and multiparity in human menopausal gonadotropin-induced intrauterine insemination cycles. Fertil Steril 56:89–92.CrossRefGoogle ScholarPubMed
Dickey, RP, Olar, TT, Taylor, SN, et al. (1992) Relationship of follicle number and other factors to fecundability and multiple pregnancy in clomiphene citrate-induced intrauterine insemination cycles. Fertil Steril 57:613–19.CrossRefGoogle ScholarPubMed
Dickey, RP, Olar, TT, Taylor, SN, et al. (1993a) Relationship of biochemical pregnancy to preovulatory endometrial thickness and pattern in ovulation induction patients. Hum Reprod 8:327–30.CrossRefGoogle Scholar
Dickey, RP, Olar, TT, Taylor, SN, et al. (1993b) Relationship of endometrial thickness and pattern to fecundity in ovulation induction cycles: effect of clomiphene citrate alone and with human menopausal gonadotropin. Fertil Steril 59:756–60.CrossRefGoogle ScholarPubMed
Dickey, RP, Olar, TT, Taylor, SN, et al. (1993c) Sequential clomiphene citrate and human menopausal gonadotropin for ovulation induction: comparison to clomiphene citrate alone and human menopausal gonadotropin alone. Hum Reprod 8:56–9.CrossRefGoogle Scholar
Dickey, RP, Taylor, NN, Lu, PY, Sartor, MM, Rye, PH, Pyrzak, R (2002) Effect of diagnosis, age, sperm quality, and number of preovulatory follicles on the outcome of multiple cycles of clomiphene citrate-intrauterine insemination. Fertil Steril 78:1088–95.CrossRefGoogle ScholarPubMed
Dickey, RP, Taylor, SN, Curole, DN, et al. (1995) Male birth rates are influenced by the insemination of unselected spermatozoa and not by clomiphene citrate. Hum Reprod 10:761–4.CrossRefGoogle Scholar
Dickey, RP, Taylor, SN, Curole, DN, et al. (1996) Incidence of spontaneous abortion in clomiphene pregnancies. Hum Reprod 11:2623–8.CrossRefGoogle ScholarPubMed
Dickey, RP, Taylor, SN, Curole, DN, et al. (1997) Relationship of dose and weight to successful outcome in clomiphene pregnancy. Hum Reprod 12:449–53.CrossRefGoogle Scholar
Dickey, RP, Taylor, SN, Lu, PY, et al. (2002). Spontaneous reduction of multiple pregnancy: incidence and effect on outcome. Am J Obstet Gynecol 186:77–83.CrossRefGoogle Scholar
Dickey, RP, Taylor, SN, Lu, PY, Sartor, BM, Pyrzak, R (2004) Clomiphene citrate intrauterine insemination (IUI) before gonadotropin IUI affects the pregnancy rate and the rate of high-order multiple pregnancies. Fertil Steril 81:545–50.CrossRefGoogle ScholarPubMed
Dickey, RP, Taylor, SN, Rye, PH, Lu, PY, Pyrzak, R (1999) Comparison of sperm quality resulting in successful intrauterine insemination to World Health Organization threshold values for normal sperm. Fertil Steril 71:684–9.CrossRefGoogle Scholar
Dickey, RP, Vorys, N, Stevens, VC, Hamwi, G, Ullery, JC (1965) Observations on the mechanism of action of clomiphene (MRL 41). Fertil Steril 16:485–94.CrossRefGoogle Scholar
DiMarzo, SJ, Kennedy, JF, Young, PE, et al. (1992) Effect of controlled ovarian hyperstimulation on pregnancy rates after intrauterine insemination. Am J Obstet Gynecol 166:1607–13.CrossRefGoogle ScholarPubMed
Downs, KA, Gibson, M (1983) Clomiphene citrate therapy for luteal phase defect. Fertil Steril 39:34.CrossRefGoogle ScholarPubMed
Eden, JA, Place, J, Carter, GD, et al. (1989) The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Obstet Gynecol 73:187–90.Google ScholarPubMed
Elnashar, A, Abdelageed, E, Fayed, M, et al. (2006) Clomiphene citrate and dexamethasone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. Hum Reprod 7:1805–8.CrossRefGoogle Scholar
Ernst, S, Hite, G, Cantrell, JS, et al. (1976) Stereochemistry of geometric isomers of clomiphene: a correction of the literature and a reexamination of structure-activity relationships. J Pharmacol Sci 65:148–50.CrossRefGoogle Scholar
Fleisher, AC, Pittaway, , Beard, , et al. (1984) Sonographic depiction of endometrial changes occurring with ovulation induction. J Ultrasound Med 3:341–6.CrossRefGoogle Scholar
Fukuma, K, Fukushima, T, Matsuo, I, et al. (1983) A graduated regimen of clomiphene citrate: its correlation to glycogen content of the endometrium and serum levels of estradiol and progesterone in infertile patients at the midluteal phase. Fertil Steril 39:780–4.CrossRefGoogle ScholarPubMed
Garcia, J, Jones, GS, Wentz, AC (1977) The use of clomiphene citrate. Fertil Steril 28:707–17.CrossRefGoogle ScholarPubMed
Glasier, AF, Irvine, DS, Wickings, EJ, et al. (1989) A comparison of the effects on follicular development between clomiphene citrate, it's two separate isomers and spontaneous cycles. Hum Reprod 4:252–6.CrossRefGoogle Scholar
Glazener, CM, Coulson, C, Lambert, PA, et al. (1990) Clomiphene treatment for women with unexplained infertility: placebo- controlled study of hormonal responses and conception rates. Gynecol Endocrinol 4:75–83.CrossRefGoogle ScholarPubMed
Gleicher, N, Oleske, DM, Tur-Kaspa, I, Vidali, A, Karande, V (2000) Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins. N Engl J Med 343:2–7.CrossRefGoogle ScholarPubMed
Greenblatt, RB, Barfield, WE, Jugck, EC, et al. (1961) Induction of ovulation with MRL/41, Preliminary Report. J Am Med Assoc 178:101–4.CrossRefGoogle ScholarPubMed
Groll, M (1984) Analysis of 700 clomiphene citrate pregnancies. Infertility 7:1–12.Google Scholar
Guzick, DS, Zeleznik, A (1990) Efficacy of clomiphene citrate in the treatment of luteal phase deficiency: quantity versus quality of preovulatory follicles. Fertil Steril 54:206–10.CrossRefGoogle ScholarPubMed
Gysler, M, March, CM, Misell, DR Jr., et al. (1982) A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test. Fertil Steril. 37:161–7.CrossRefGoogle ScholarPubMed
Hammond, MG, Halme, JK, Taubert, LM (1983) Factors affecting the pregnancy rate in clomiphene citrate induction of ovulation. Obstet Gynecol 62:196–202.Google ScholarPubMed
Hammond, MG, Taubert, LM (1982) Clomiphene citrate therapy of infertile women with low luteal phase progesterone levels. Obstet Gynecol 59:275–9.Google ScholarPubMed
Harman, PJ, Blackman, GL (1981) High-performance liquid chromatographic determination of clomiphene using post-column online photolysis and fluorescence detection. J Chromatogr 225;131–8.CrossRefGoogle Scholar
Hoffman, D, Lobo, RA (1985) Serum dehydroepiandrosterone sulfate and the use of clomiphene citrate in anovulatory women. Fertil Steril 43:196–9.CrossRefGoogle ScholarPubMed
Holtkamp, (1984) Cited in Corson SL, Batzer FR, Alexander NJ, et al. (1984). Sex selection by sperm separation and insemination. Fertil Steril 42:756–60.Google Scholar
Holtkamp, (1987) Research and development of clomiphene citrate. In Asch, RH et al. eds. Recent Advances in Human Reproduction. Fondazione Per Gli Studi Sulla Riproduzione Umana, Stampato d'alla, Maggio, Italy, pp. 17–27.Google Scholar
Holtkamp, , Greslin, JG, Root, CA, et al. (1960) Gonadotropin inhibiting and anti-fecundability effects of chloramiphene. Proc Soc Exp Biol Med 105:197–201.CrossRefGoogle ScholarPubMed
Hsueh, AJW, Erickson, GF, Yen, SSC (1978) Sensitization of pituitary cells to luteinizing hormone releasing hormone by clomiphene citrate in vitro. Nature 273:57–9.CrossRefGoogle Scholar
Huang, K-E (1986) The primary treatment of luteal phase inadequacy: progesterone versus clomiphene citrate. Am J Obstet Gynecol 155:824–8.CrossRefGoogle ScholarPubMed
Imoedemhe, DA, Shaw, RW, Kirkland, A, et al. (1987) Ultrasound measurement of endometrial thickness on different ovarian stimulation regimens during in vitro fertilization. Hum Reprod 2:545–7.CrossRefGoogle ScholarPubMed
Isaacs, JD Jr., Lincoln, SR, Cowan, BD (1997) Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone. Fertil Steril 67:641–3.CrossRefGoogle Scholar
James, WH (1980) Gonadotropin and the human secondary sex ration. Br Med J 281:711–12.CrossRefGoogle Scholar
James, WH (1985) The sex ratio of infants born after hormonal induction of ovulation. Br J Obstet Gynecol 92:299–301.CrossRefGoogle ScholarPubMed
Jansen, RPS (1982) Spontaneous abortion incidence in the treatment of infertility. Am J Obstet Gynecol 143:451–73.CrossRefGoogle ScholarPubMed
Kauffman, RP, Baker, VM, DiMarino, P, et al. (2002) Polycystic ovarian syndrome and insulin resistance in white and Mexican American women: a comparison of two distinct populations. Am J Obstet Gynecol 187:1362–9.CrossRefGoogle ScholarPubMed
Kemman, E, Bohrer, M, Shelden, R, et al. (1987) Active ovulation management increases the monthly probability of pregnancy occurrence in ovulatory women who receive intrauterine insemination. Fertil Steril 48:916–20.CrossRefGoogle Scholar
Kerin, JF, Liu, JH, Phillipou, G, Yen, SSC (1985) Evidence for a hypothamlamic site of action of clomiphene citrate in women. J Clin Endocrinol Metab 61:265–8.CrossRefGoogle ScholarPubMed
Kistner, RW (1966) Use of clomiphene citrate, human chorionic gonadotropins and human menopausal gonadotropins for induction of ovulation in the human female. Fertil Steril 17;569–83.CrossRefGoogle ScholarPubMed
Kocak, M, Caliskan, E, Simsir, C, et al. (2002) Metformin therapy improves ovulatory rates, cervical scores and pregnancy rates in clomiphene citrate resistant women with polycystic ovary syndrome. Fertil Steril 77:101–6.CrossRefGoogle ScholarPubMed
Kurachi, K, Aono, T, Minagawa, J, et al. (1983) Congenital malformations of newborn infants after clomiphene-induced ovulation. Fertil Steril 40:187–9.CrossRefGoogle ScholarPubMed
Legro, RS, Finegood, D, Dunaif, A (1998) A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 83;2694–8.Google ScholarPubMed
Lobo, RA, Granger, LR, Davajan, V, Mishell, DR (1982a) An extended regimen of clomiphene citrate in women unresponsive to standard therapy. Fertil Steril 37:762–6.CrossRefGoogle ScholarPubMed
Lobo, RA, Paul, W, March, CM, et al. (1982b) Clomiphene and dexamethasone in women unresponsive to clomiphene alone. Obstet Gynecol 60:497–501.Google ScholarPubMed
Macgregor, AH, Johnson, JE, Bunde, CA (1967) Induction of ovulation with clomiphene citrate. Presented at the 14th Annual Meeting of the Canadian Society for the Study of Fertility, Montreal, June 19–21.Google Scholar
Macgregor, AH, Johnson, JE, Bunde, CA (1968) Further clinical experience with clomiphene citrate. Fertil Steril 19:616–22.CrossRefGoogle ScholarPubMed
Maclin, VM, Radwanska, E, Binor, Z, et al. (1990) Progesterone: estradiol ratios at implantation in ongoing pregnancies, abortions, and nonconception cycles resulting from ovulation induction. Fertil Steril 54:238–44.CrossRefGoogle ScholarPubMed
Marchbanks, PA, Coulam, CB, Annegers, JF (1986) An association between clomiphene citrate and ectopic pregnancy: a preliminary report. Fertil Steril 44:268–70.CrossRefGoogle Scholar
Marchini, M, Dorta, M, Bombelli, F, et al. (1989) Effects of clomiphene citrate on cervical mucus: analysis of some influencing factors. Int J Fertil 34:154–9.Google ScholarPubMed
Marrs, RP, Vargas, JM, Shangold, GM, et al. (1984) The effect of time of initiation of clomiphene citrate on multiple follicle development for human in vitro fertilization and embryo replacement procedures. Fertil Steril 41:682–5.CrossRefGoogle ScholarPubMed
Martinez, AR, Bernardus, RE, Voorhorst, FJ, et al. (1990) Intrauterine insemination does and clomiphene citrate does not improve fecundity in couple with infertility due to male or idiopathic factors: a prospective, randomized, controlled study. Fertil Steril 53:847–53.CrossRefGoogle ScholarPubMed
Melis, GB, Paoletti, AM, Strigini, F, et al. (1987) Pharmacologic induction of multiple follicular development improves the success rate of artificial insemination with husband's semen in couples with male-related or unexplained infertility. Fertil Steril 47:441–5.CrossRefGoogle ScholarPubMed
Mikkelson, TJ, Kroboth, PD, Cameron, WJ, et al. (1986) Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. Fertil Steril 46:392–6.CrossRefGoogle ScholarPubMed
Murthy, YS, Parekh, MC, Arronet, GH (1971) Experience with clomiphene and cisclomiphene. Int J Fertil 16:66–74.Google ScholarPubMed
Nestler, JE, Jakubowics, DJ, Evans, WS, et al. (1998) Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 338:1876–80.CrossRefGoogle ScholarPubMed
Palopoli, FP, Feil, VJ, Allen, RE et al. (1967) Substituted aminoalkoxytriarylhodoethylenes. J Med Chem 10:84–7.CrossRefGoogle Scholar
Parsanezhad, ME, Albozi, S, Motazedian, S, et al. (2002) Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels; a prospective, double-blind, placebo-controlled trial. Fertil Steril 78:1001–4.CrossRefGoogle Scholar
Pildes, RB (1965) Induction of ovulation with clomiphene. Am J Obstet Gynecol 91:466–73.CrossRefGoogle ScholarPubMed
Powell-Phillips, WD (1979) Clomiphene citrate induced concurrent ovarian and intrauterine pregnancy. Obstet Gynecol 53:37–9.Google Scholar
Quigley, MM, Berkowitz, AS, Gilbert, SA, et al. (1984) Clomiphene citrate in an in vitro fertilization program; hormonal comparisons between 50- and 150-mg dosages. Fertil Steril 41:809–15.CrossRefGoogle Scholar
Randall, JM, Templeton, AT (1991) Transvaginal sonographic assessment of follicular and endometrial growth in spontaneous and clomiphene citrate cycles. Fertil Steril 56:208–12.CrossRefGoogle ScholarPubMed
Rizk, B (2006) Epidemiology of ovarian hyperstimulation syndrome. In Rizk, B. (ed.), Ovarian Hyperstimulation Syndrome. Cambridge: United Kingdom, Cambridge University Press, chapter 2, 10–42.Google Scholar
Rizk, B (Ed.) (2008) Ultrasonography in Reproductive Medicine and Infertility. Cambridge: United Kingdom, Cambridge University Press, (in press).Google Scholar
Rizk, B, Dickey, RP (2008) Ovarian Hyperstimulation Syndrome. In Dickey, RP, Brinsden, PRPyrzak, R (Eds.) Intrauterine Insemination. Cambridge: United Kingdom, Cambridge University Press, (in press).Google Scholar
Rogers, PA, Polson, D, Murphy, CR, et al. (1991) Correlation of endometrial histology, morphometry, and ultrasound appearance after different stimulation protocols for in vitro fertilization. Fertil Steril 55:583–7.CrossRefGoogle ScholarPubMed
Rossing, MA, Daling, JR, Weiss, NS, et al. (1994) Ovarian tumors in a cohort of infertile women. N Engl J Med 331:771–6.CrossRefGoogle Scholar
Schneider, L, Bessis, R, Simmonet, T (1979) The frequency of ovular resorption during the first trimester of twin pregnancy. Acta Genet Med Gemollol 28:271–2.Google ScholarPubMed
Scott, RT, Hofmann, GE (1995) Prognostic assessment of ovarian reserve. Fertil Steril 63:1–11.CrossRefGoogle ScholarPubMed
Shalev, J, Goldenberg, M, Kukia, E, et al. (1989) Comparison of five clomiphene citrate dosage regimens: follicular recruitment and distribution in the human ovary. Fertil Steril 52:560–3.CrossRefGoogle ScholarPubMed
Shepard, MK, Balmaceda, JP, Leija, CG (1979) Relationship of weight to successful induction of ovulation with clomiphene citrate. Fertil Steril 32:641–5.CrossRefGoogle ScholarPubMed
Steinkampf, (2008) Ultrasonography for Computing Controlled Ovarian Hyperstimulation. In Rizk, B. (ed.), Ultrasonography in Reproductive Medicine and Infertility. Cambridge: United Kingdom, Cambridge University Press, (in press).
Sterzik, K, Dallenbach, C, Scneider, V, et al. (1988) In vitro fertilization: the degree of endometrial insufficiency varies with the type of ovarian stimulation. Fertil Steril 50:457–62.CrossRefGoogle ScholarPubMed
Taubert, HD, Dericks-Tan, JSE (1976) High doses of estrogens do not interfere with the ovulation-inducing effect of clomiphene citrate. Fertil Steril 27:375–82.CrossRefGoogle Scholar
Trott, EA, Plouffe, L Jr., Hansen, K, et al. (1996) Ovulation induction in clomiphene resistant anovulatory women with normal dehydroepiandrosterone sulfate levels; beneficial effects of the addition of dexamethasone during the follicular phase. Fertil Steril 66:484–7.CrossRefGoogle ScholarPubMed
Tyler, ET, Winer, J, Gotlib, M, et al. (1962) Effects of MRL-41 in human male and female fertility studies (Abstr). Clin Res 10:119.Google Scholar
Campenhout, J, Simard, R, Leduc, B (1968) Antiestrogen effect of clomiphene in the human being. Fertil Steril 19:700–6.CrossRefGoogle Scholar
Vandermolen, DT, Ratts, VS, Evans, WS, et al. (2000) Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril 75: 310–15.CrossRefGoogle Scholar
Vorys, N, Gantt, CL, Hamwi, IGJ, et al. (1964) Clinical utility of chemical induction of ovulation. Am J Obstet Gynecol 88:425–32.CrossRefGoogle ScholarPubMed
Whittemore, AS, Harris, R, Intyre, J, et al. (1992) Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. Am J Epidemiol 136:1184–203.CrossRefGoogle ScholarPubMed
World Health Organization, (1992) World Health Organization Laboratory Manual for the Examination of Human Sperm-Cervical Mucus Interaction. Cambridge University Press, Cambridge, pp. 43–44.Google Scholar
Yagel, S, Ben-Chetrit, A, Anteby, E, et al. (1992) The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertil Steril 57:33–6.CrossRefGoogle ScholarPubMed
Yanagimachi, R, Sato, A (1986) Effects of a single oral administration of ethinyl estradiol on early pregnancy in the mouse. Fertil Steril 19:787–801.CrossRefGoogle Scholar
Young, RL, Goldzieher, JW, Elkind-Hirsch, K, et al. (1991) A short-term comparison of the effects of clomiphene citrate and conjugated equine estrogen in menopausal/castrate women. Int J Fertil 36:167–71.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
×