Clinical trial NCT02690870: Tamoxifen and Clomiphene Citrate in Mild Stimulation IVF
Official title: Comparison of Tamoxifen and Clomiphene Citrate in Mild Stimulation IVF: a Prospective Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Infertility
Keywords: tamoxifen
clomiphene
mild stimulation
poor ovarian response
clinical pregnancy rate
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
First posted: 2016-02-24
Enrollment: 210
Sex: FEMALE
Minimum age (years): 37
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective cohort study is to compare IVF outcome between tamoxifen and clomiphene citrate in mild stimulation.

Detailed description: The reported prevalence of poor ovarian responders amongst patients undergoing IVF-ET is 9%-24%, and morbidity must be higher nowadays. For these women, Mild stimulation has been an important ovulation induction protocol. Clomiphene citrate(CC) and tamoxifen(TMX) are commonly used in mild stimulation protocol. It's reported that CC has adverse effect on growth of endrometrium and results in thin endrometrium(≤7mm) which maybe affect pregnancy rate. However, TMX has estrogen-like effect on the endrometrium that may be helpful to increase endormetrial thickness. The reported results about comparing CC with TMX showed that they had similar ovulation rate. Prospective study is necessary to confirm whether TMX is superior to CC on the IVF outcome.

Eligibility criteria: Inclusion Criteria:

1. age between 37 and 42;
2. BMI≤23kg/m2;
3. ≤3 oocytes with a conventional stimulation protocol;
4. AFC\<5 follicles or AMH\<1.1 ng/ml on the day 1 to 5 of the menses;
5. Cause of Infertiity: tubal factor, male factor, diminished ovarian reserve.

Exclusion Criteria:

1. endormetrial polyp, endormetrial cancer,intrauterine adhesions,uterine fibroids that affects uterine cavity
2. Endometriosis, adenomyosis
3. The diameter of Hydrosalpinx \>2cm

Primary outcomes:
measure: clinical pregnancy rate
timeFrame: four weeks after embryo transfer
Secondary outcomes:
measure: cycle cancellations for thin endrometrial thickness
timeFrame: on the HCG day
measure: endrometrial pattern and thickness on the day of HCG administration
timeFrame: on the HCG day
measure: the number of follicular diameter≥10mm and sexual hormone test on the HCG day
timeFrame: on the HCG day
Other outcomes:
Locations:
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Qingxue ZHANG
role: STUDY_DIRECTOR
References:
citation: Boostanfar R, Jain JK, Mishell DR Jr, Paulson RJ. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril. 2001 May;75(5):1024-6. doi: 10.1016/s0015-0282(01)01749-6.
citation: Revelli A, Casano S, Salvagno F, Delle Piane L. Milder is better? Advantages and disadvantages of "mild" ovarian stimulation for human in vitro fertilization. Reprod Biol Endocrinol. 2011 Feb 16;9:25. doi: 10.1186/1477-7827-9-25.
citation: Badawy A, Gibreal A. RETRACTED: Clomiphene citrate versus tamoxifen for ovulation induction in women with PCOS: a prospective randomized trial. Eur J Obstet Gynecol Reprod Biol. 2011 Nov;159(1):151-154. doi: 10.1016/j.ejogrb.2011.07.015. Epub 2011 Aug 9. No abstract available.
citation: Wang CW, Horng SG, Chen CK, Wang HS, Huang HY, Lee CL, Soong YK. Ovulation induction with tamoxifen and alternate-day gonadotrophin in patients with thin endometrium. Reprod Biomed Online. 2008 Jul;17(1):20-6. doi: 10.1016/s1472-6483(10)60288-x.
citation: Reynolds K, Khoury J, Sosnowski J, Thie J, Hofmann G. Comparison of the effect of tamoxifen on endometrial thickness in women with thin endometrium (<7mm) undergoing ovulation induction with clomiphene citrate. Fertil Steril. 2010 Apr;93(6):2091-3. doi: 10.1016/j.fertnstert.2009.08.038. Epub 2009 Sep 22.
citation: Brinton LA, Westhoff CL, Scoccia B, Lamb EJ, Trabert B, Niwa S, Moghissi KS. Fertility drugs and endometrial cancer risk: results from an extended follow-up of a large infertility cohort. Hum Reprod. 2013 Oct;28(10):2813-21. doi: 10.1093/humrep/det323. Epub 2013 Aug 13.
citation: Ozcan Cenksoy P, Ficicioglu C, Kizilkale O, Suhha Bostanci M, Bakacak M, Yesiladali M, Kaspar C. The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Gynecol Endocrinol. 2014 Jul;30(7):485-9. doi: 10.3109/09513590.2014.893571. Epub 2014 Mar 5.
citation: Pourmatroud E, Zargar M, Nikbakht R, Moramazi F. A new look at tamoxifen: co-administration with letrozole in intrauterine insemination cycles. Arch Gynecol Obstet. 2013 Feb;287(2):383-7. doi: 10.1007/s00404-012-2556-3. Epub 2012 Sep 25.
citation: Mazzarino M, Biava M, de la Torre X, Fiacco I, Botre F. Characterization of the biotransformation pathways of clomiphene, tamoxifen and toremifene as assessed by LC-MS/(MS) following in vitro and excretion studies. Anal Bioanal Chem. 2013 Jun;405(16):5467-87. doi: 10.1007/s00216-013-6961-7. Epub 2013 Apr 23.
citation: Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E. Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD002249. doi: 10.1002/14651858.CD002249.pub4.
citation: Zakherah MS, Nasr A, El Saman AM, Shaaban OM, Shahin AY. Clomiphene citrate plus tamoxifen versus laparoscopic ovarian drilling in women with clomiphene-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2010 Mar;108(3):240-3. doi: 10.1016/j.ijgo.2009.10.004. Epub 2009 Nov 26.
citation: Steiner AZ, Terplan M, Paulson RJ. Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005 Jun;20(6):1511-5. doi: 10.1093/humrep/deh840. Epub 2005 Apr 21.
citation: Wang HS, Wang TH, Soong YK. Cyclic changes in serum levels of insulin-like growth factor binding protein-1 in women treated with clomiphene citrate and tamoxifen. Gynecol Endocrinol. 2000 Aug;14(4):236-44. doi: 10.3109/09513590009167687.
citation: Mazzarino M, Bragano MC, de la Torre X, Molaioni F, Botre F. Relevance of the selective oestrogen receptor modulators tamoxifen, toremifene and clomiphene in doping field: endogenous steroids urinary profile after multiple oral doses. Steroids. 2011 Nov;76(12):1400-6. doi: 10.1016/j.steroids.2011.06.005. Epub 2011 Jun 30.