Comparison of efficacy of Clomiphene Citrate and Tamoxifen for induction
of Ovulation among women with Anovulatory Infertility
Padma Raj Pant
Department of Obstetrics and Gynaecology, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal. Background:Infertility is a global problem among the married couple. Globally 10 to 15 percent of the couples are experiencing this
problem. Anovulation is one of the major causes of infertility. Clomiphene citrate and tamoxifen- both drugs are selective estrogen receptor modulators. In women with anovulatory infertility, both of these drugs have been used for induction of ovulation. This study compared the efficacy of these drugs for induction of ovulation, endometrial response and pregnancy rates.
Methods: A prospective, comparative study conducted in infertility clinic of Tribhuvan University, Kathmandu. Women who failed to
develop dominant follicle for consecutive three cycles were considered as anovulatory. In 200 such women ovulation was induced withclomiphene (100 cases, group A) and tamoxifen(100 cases, group B).Selection of the women in these two groups was done blindly, picking up the envelope containing chit, written A or B. Dose of clomiphene ranged from 50-150 mg and that of tamoxifen 20- 60mg.Follicular monitoring was done by transvaginalultrasonogram from 9 day of the cycle. Development of follicle, endometrial response, ovulation rate and pregnancy rate recorded and analyzed.
Results: In group A women,endometrial thickness decreased with increase in the dose of drug, but in groupB women, endometrial
thickness increased with increase in the dose of tamoxifen. Ovulation occurred 63 % in group A and 61 % group B.Pregnancy rate was 17% among groupA and 21% among group B.
Conclusion: Tamoxifen is an equally effective alternative for induction of ovulation.
Key words: clomiphene citrate,tamoxifen, ovulation induction.
Materials and methods
Ovulation is a core event for reproduction. This was a prospective, comparative study, Among the causes of infertility, 20-25 % accounts for done on two hundred women with anovulatory anovulation[1]. Clomiphene citrate (cc) is most infertility attending infertility clinic of Tribhuvan widely used drug for induction of ovulation. University, Teaching Hospital Kathmandu. Duration Pregnancy rate with clomiphene citrate is 30-40 %, of the study was two years from August 2007 to July but ovulation rate of 70-80% [2].The disparity 2009. History of all the couple with primary between ovulation and pregnancy rate may be due to infertility wastaken in detail. Couple were examined, antiestrogenic action of CC on endometrium and counseled and investigated. Thyroid disorders, cervical mucus. Tamoxifen (TMX)is another drug hyperprolactinemia, abnormal levels of follicle similar in structure to clomiphene and is used for stimulating and luteinizing hormone levels were induction of ovulation with reported ovulation rate of ruled out. Tubal patency test was done by hystero- 50-90% and pregnancy rate30-50%[3,4,5].The better salpingogram (HSG). Husband's semen analysis was ovulation and pregnancy rates with tamoxifen may be done. Follicular monitoring was done by transvaginal due to higher score on endometrium and cervical sonogram (TVS) from 9th day of the menstrual cycle. mucus and better functioning corpus luteum [3,6].
Absence of development of dominant follicle (18-22 Address for correspondence
Dr. Padama Raj Pant
Professor, Dept. of Obstetrics and Gnyaecology, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal.
E- mail: [email protected]
Medica Innovatica June 2013 Volume 2 Issue 1 68 Pant, et al,: Comparison of efficacy of clomiphene citrate and tamoxifen for induction of ovulation mm) in three consecutive menstrual cycles by TVS was considered as anovulatory infertility. These women with anovulatory infertility were again counseled and written consent was taken from those who agreed to be enrolled in the study.Women with anovulatory infertility were divided in two groups.In women of Group A, ovulation was induced with clomiphene citrate, starting from 50mg to 150 mg/day from second day of cycle for 5 days. Clomiphene was given 50 mg/day in first cycle. If there was no adequate sizefollicular development the dose was increased in next cycle. Clomiphene was repeated maximum for 6 cycles.In Group B women, the ovulation induction was done with tamoxifen 20-60 mg /day from the same day of menstrual cycle and same duration as clomiphene.
Exclusion criteria
Women with bilateral tubal block, those husbands were oligo or azoospermic, women below 20 or above 40 years of age, anovulation class 3 (hypergonadotrophic-hypogonadism), women with active liver disease,diagnosed case of Asherman's syndrome,hyperprolactinemia,thyroid dysfunction, secondary infertility,diagnosed cases of myoma uteri,endometriosis, ovarian tumor, hydro- or pyosalpinx, pelvic tuberculosis,genital tract anomaly, history of chemo or radiotherapy, conization of the cervix, on antipsychotic, anti-hypertensive, antiemetic drugs or hormones.
As shown in figure 1and 2 endometrial thickness was 8-13 mm in 91 percent Figure 1 and 2. Response of endometrium to
patients when clomiphene was given 50 mg.With different doses of clomiphene citrate and tamoxifen
increase in dose, percentage of women with this thickness of endometrium decreased. In tamoxifen group, some of the women had endometrial thickness more than 14 mm with 40 and 60 mg of the drug.
Medica Innovatica June 2013 Volume 2 Issue 1 Pant, et al,: Comparison of efficacy of clomiphene citrate and tamoxifen for induction of ovulation Figure 3. Drug doses and adequate follicle formation
Comparison of efficacy of two drugs in tamoxifen group, LH surge was positive in 62 % and relation to the adequate size folliclular development 61 % cases respectively with p value of 0.76 (Figure with different doses: (figure 2) While inducing ovulation with clomiphene citrate, 32 % of women Biochemical pregnancy when compared had development of adequate size follicle after taking between CC 50 mg and TMX 20 mg, p value is 0.42; 50 mg of the drug in first time. Some of the women 100mg CC and 40 mg TMX, p value is 0.07; 150mg who had adequate size follicular development after CC and 60 mg TMX, p value is 0.75 Clinical taking 50 mg of clomiphene could not conceive. Some pregnancy, when compared between CC 50 mg and of them needed increased dose of the drug. From these TMX 20 mg, p value is 0.12; 100mg CC and 40 mg failures and rest 68 percent who did not respond to 50 TMX, p value is 0.05; 150mg CC and 60 mg TMX, p mg clomiphene,44 % responded to 100 mg. Similarly, failures from these two groups, a total of 65% women Table1. Comparison of biochemical and clinical pregnancy rates.
had development of adequate size follicle after taking Discussion
150 mg of the drug. In the same way, in Tamoxifen Clomiphene citrate is the drug used first for group 29 % responded to 20 mg, 39 and 63 percent ovulation induction in women with anovulatory women responded to 40 mg and 60 mg respectively. infertility. Later on many other drugs like metformin, Though there was adequate size follicle formation in tamoxifen, bromocriptine, and gonadotropin are 65 % cases of clomiphene and 63 % cases of being used for this purpose.
Medica Innovatica June 2013 Volume 2 Issue 1 70 Pant, et al,: Comparison of efficacy of clomiphene citrate and tamoxifen for induction of ovulation Clomiphene and tamoxifen are of same group 4. GulekliB,OzaksitG,TurhanNO,SenozS,Oral of drugs but tamoxifen has been used for ovulation H, Gokman O. Tamoxifen an alternative induction only since last few years and there are not approach in clomiphene resistant polycystic many studies for comparison of efficacy of these two ovarian syndrome patients. J Pak Med Assoc.1993; 43: 89-91.
Though it is assumed that the women with 5. Williamson JG, Ellis JD. The induction of regular menstrual cycles of 28-30 days are considered ovulation by tamoxifen. J Obstetric Gynaecol as ovulatory, but in this study, 28 percent of women Brit Commonw.1973; 80:844-7.
with anovulation had regular menstrual cycle of 28-30 6. Roumen ME, Doesburg HW, Rolland R. days. Women older than 35 years had less conception Treatment of infertile women with a deficient rate in both groups but the endometrial thickness was post-coital test with two antiestrogens: better in Tamoxifen group.
Clomiphene and tamoxifen. FertilSteril. Robert Boostanfar, in a similar study [7], 1984; 41:237-43.
found 46% ovulation rates in Clomiphene group and 7. Boostanfar R,Jain JK,Mishell JR,Paulsom 56.5 % in Tamoxifen group in comparison to 32 and 21 RJ. A prospective randomized trial comparing percent in this study. Cumulative pregnancy rate clomiphene citrate with tamoxifen citrate for according to Boostanfar was 14.6 % and in this study it ovulation induction. Fertil Steril 2001 May; According to another study done by Greenblat 8. Greenblat RB, Barfield WE, Jungck EC and also the ovulation rates were quite higher than this Ray AW. Induction of Ovulation with study which was 80 and 40 % in Clomiphene and MRL/41, primary report. J Am Med Tamoxifen group respectively [8]. According to a Assoc1961; 178-80.
meta-analysis done by Anne Z Steiner and co- 9. Steiner AZ, Terplan M, Paulson RJ. workers, Tamoxifen is equally effective as Comparison of tamoxifen and clomiphene clomiphene for induction of ovulation [9]. But Ruiz- citrate for ovulation induction: a meta- velasco V and co-worker found better ovulation rate in analysis. Hum Reprod 2005 Jun; 20(6): 1511- Tamoxifen group; 85.99% ovulation and 35.5 % pregnancy rate in clomiphene and 95% and 35.5% in 10. Ruiz-Velasco V, Rosas-Arcoe J, Matute MM. tamoxifen group [10]. None of the studies had Chemical inducers of ovulation: comparative mentioned about the endometrial responses to these results. Int. J Fertil.1979; 24(1):61-4.
drugs. Hence, it can be concluded that tamoxifen is an equally effective alternative for induction of ovulation. How to cite this
article Pant PR.
1. Rowlend M. Infertility therapy. Effect of Comparsion of efficacy of clomiphene citrate innovations and increasing experience. J and tamoxifen for induction of ovulation reproductive Med 1980; 25: 42-5.
among women with anovulatory infertility. 2. Wu CH. A practical approach to clomiphene Med Inn 2013;2:68-71.
therapy. Clin Obstetric.Gynecol1984;27:935- Source of funding - Nil
Conflict of interest - None declared
3. Borenstein R, Shoham Z, Yemini M, Barash A, Fienstein M, Rozenman D. Tamoxifen treatment in women with failure of clomiphene citrate therapy.Austr NZ J Obstetric Gynaecol 1989;29:173-5.
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