Spontaneous pregnancy after clomiphene citrate failure

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Spontaneous pregnancy after clomiphene citrate failure
  BRIEF COMMUNICATION Spontaneous pregnancy after clomiphenecitrate failure M. Sayyah Melli, A. Gasemzadeh, M. Alizadeh * Department of Obstetrics and Gynecology, Alzahra Research and Development Center of Clinical Studies,Tabriz Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Received 9 March 2005; received in revised form 31 May 2005; accepted 1 June 2005 Chronic anovulation is a frequent cause of infer-tility, and treatment with antiestrogen clomiphenecitrate (CC) is considered successful [1]. Theeffect of CC on follicle development is not known.If an anovulatory woman becomes pregnant duringthe treatment cycle, the result is caused by theaction of the drug, but if pregnancy occurs afterCC administration, it may be due to a residualeffect. Clomiphene is a racemic mixture of 2stereoisomers, enclomiphene ( E  -isomer) andzuclomiphene ( Z  -isomer).  E  -isomer, the morepotent, but with a short half-life, is responsiblefor the ovulation-inducing action of clomiphene. Z  -isomer is cleared much more slowly; serumlevels remain detectable for weeks after a singledose, and may accumulate over a series of treatment cycles [2].The purpose of this study was to determine therate of spontaneous pregnancies 1 month afterending therapy with clomiphene citrate 50 mg(Clomid; Iran Hormone Company, Tehran, Iran),and to evaluate its relation to the number and sizeof follicles and to the endometrial thickness in thenext menstrual cycle.From March 2001 to September 2004, 306anovulatory women were included in the study(Fig. 1). The overall pregnancy rate was 31.2%(23%, 35%, and 20%, respectively) for three con-secutive rest periods between treatment withclomiphene citrate. The number of follicles isshown in Table 1. Mean endometrial thickness wasincreased after each treatment cycle (Table 2).Clomiphene citrate could stimulate follicles todevelop in menstrual cycles during which the drug isnot administered [3]. It has been considered that follicle recruitment in normal cycles begins in theluteal phase of the previous cycle, but, according toother studies, follicular development starts 85 daysbefore the cycle inwhich ovulation occurs.When CChas accomplished its mission, it is possible that it 0020-7292/$ - see front matter  D  2005 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.All rights reserved.doi:10.1016/j.ijgo.2005.06.011* Corresponding author. Tel.: +98 411 336 4673; fax: +98 411336 4668. E-mail addresses:  alizadehm@tbzmed.ac.ir,alizadm@yahoo.com (M. Alizadeh).International Journal of Gynecology and Obstetrics (2005)  91 , 179—181 KEYWORDS Clomiphene failure;Anovulation;Spontaneouspregnancy www.elsevier.com/locate/ijgo  performs its duty several times before it is cleared[4]. In this study, there was no significant relationbetween the last administration of CC and thepregnancy rate during the first and second restintervals.The pregnancies achieved in the cycle subse-quent to treatment with CC could be due to aresidual effect on gonadotropine secretion, and toa stimulatory effect of CC via negative feedback tothe hypothalamic—pituitary axis, causing de-creased antiestrogen activity on the endometriumand cervical mucus. Leaving the hormonal systemat rest after a mild or moderate stimulation, anyemotional stress might facilitate spontaneous ovu-lation and pregnancy. This study suggests schedul-ing an interval between treatment courses. Trial 1 First-month treatment50 mg (100%) n=306 Second-month treatment50 mg (41.2%) or 100 mg (58.8%) n=278 One-month restn=250 Trial 2 First-month treatment50 mg (21.8%), 100 mg (77.8%), or 150 mg (0.4%) n=227 Second-month treatment50 mg (5.3%),100 mg (82.2%),or 150 mg (12.4%) n=194One-month restn=163 Trial 3 First-month treatment50 mg (4.2%), 100 mg (67.7%), or 150 mg (28.1%) n=128 Second-month treatment50 mg (1%), 100 mg (36.1%), 150 mg (62.8%) n=102 One-month restn=92 Did not conceive Did not conceive Did not conceive Did not conceive Did not conceive Did not conceive Did not conceiveConceived, excluded n=28 Conceived, included n=23Conceived, excludedn=28 Conceived, excludedn=25 Conceived, Includedn=35Conceived, excludedn=31 Conceived, excludedn=26 Conceived, includedn=20 Conceived, excludedn=12 Did not conceive Figure 1  Flow of patients. M. Sayyah Melli et al.180  References [1] Dickey RP, Holtkamp DE. Development, pharmacology andclinical experience with clomiphene citrate. Hum ReprodUpdat 1996;2:483–506.[2] Young SL, Opsahl MS, Fritz MA. Serum concentrations of enclomiphene and zuclomiphene across consecutive cyclesof clomiphene citrate therapy in anovulatory infertilewomen. Fertil Steril 1999;71:639–44.[3] Opsahl MS, Robins ED, O’Connor DM, Scott RT, Fritz MA.Characteristics of gonadotropine response, follicular devel-opment, and endometrial growth and maturation acrossconsecutive cycles of CC treatment. Fertil Steril 1996;66:533–9.[4] Haritha S, Rajacopalan G. Follicular growth, endometrialthickness, and serum estradiol levels in spontaneous andclomiphene citrate-induced cycles. Int J Gynecol Obstet2003;81:287. Table 1  Mean number of follicles after each dose inthree trials Trial Mean number of folliclesFirst dose (mm) Second dose (mm)  P   valueTrial 1 1.47 (1.39—1.54) a 2.36 (2.23—2.49) 0.0001Trial 2 2.38 (1.52—4.13) 3.59 (2.26—4.86) 0.0001Trial 3 2.96 (2.84—3.08) 3.63 (3.44—3.18) 0.0001 a 95% confidence interval. Table 2  Mean endometrial thickness after threetrials Trial Mean thickness of endometriumFirst dose (mm) Second dose (mm)  P   valueTrial 1 6.28 (6.04—6.52) a 7.77 (7.53—8.02) 0.0001Trial 2 7.84 (7.61—8.08) 8.82 (8.59—9.05) 0.0001Trial 3 9.12 (8.88—9.37) 9.41 (9.17—9.64) 0.0001 a 95% confidence interval. Spontaneous pregnancy after clomiphene citrate failure 181
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