Follicle stimulating hormone versus clomiphene citrate in intrauterine insemination for unexplained subfertility: a randomized controlled trial

被引:31
作者
Danhof, N. A. [1 ]
van Wely, M. [1 ]
Repping, S. [1 ]
Koks, C. [2 ]
Verhoeve, H. R. [3 ]
de Bruin, J. P. [4 ]
Verberg, M. F. G. [5 ]
van Hooff, M. H. A. [6 ]
Cohlen, B. J. [7 ]
van Heteren, C. F. [8 ]
Fleischer, K. [9 ]
Gianotten, J. [10 ]
van Disseldorp, J. [11 ]
Visser, J. [12 ]
Broekmans, F. J. M. [13 ]
Mol, B. W. J. [14 ]
van der Veen, F. [1 ]
Mochtar, M. H. [1 ]
机构
[1] Acad Med Ctr, Ctr Reprod Med, Meiberg Dreef 9, NL-1105 AZ Amsterdam, Netherlands
[2] Maxima Med Ctr, Dept Obstet & Gynaecol, Postbus 7777, NL-5500 MB Veldhoven, Netherlands
[3] OLVG Oost, Dept Obstet & Gynaecol, Oosterpk 9, NL-1091 AC Amsterdam, Netherlands
[4] Jeroen Bosch Hosp, Dept Obstet & Gynecol, Postbus 90153, NL-5200 ME Shertogenbosch, Netherlands
[5] Fertil Clin Twente, Demmersweg 66, NL-7556 BN Hengelo, Netherlands
[6] St Franciscus Gasthuis, Dept Obstet & Gynaecol, Kleiweg 500, NL-3045 PM Rotterdam, Netherlands
[7] Isala Hosp, Dept Obstet & Gynecol, Postbus 10400, NL-8000 GK Zwolle, Netherlands
[8] Canisius Wilhelmina Hosp, Dept Obstet & Gynaecol, Postbus 9015, NL-6500 GS Nijmegen, Netherlands
[9] Radboud Univ Nijmegen, Med Ctr, Ctr Reprod Med, Geert Grootepl Zuid 10, NL-6525 GA Nijmegen, Netherlands
[10] Spaarne Gasthuis, Dept Obstet & Gynaecol, Postbus 417, NL-2000 AK Haarlem, Netherlands
[11] St Antonius Hosp Nieuwegein, Dept Obstet & Gynaecol, Koekoekslaan 1, NL-3435 CM Nieuwegein, Netherlands
[12] Dept Obstet & Gynaecol Amphia, Postbus 90157, NL-4800 RL Breda, Netherlands
[13] Univ Med Ctr Utrecht, Ctr Reprod Med, Postbus 85500, NL-3508 GA Utrecht, Netherlands
[14] Monash Univ, Monash Med Ctr, 246 Clayton Rd, Clayton, Vic 3168, Australia
关键词
IUI; ovarian stimulation; FSH; clomiphene citrate; unexplained subfertility; cancellation criteria; SPONTANEOUS PREGNANCY; COUPLES; PREDICTION;
D O I
10.1093/humrep/dey268
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
STUDY QUESTION: Is FSH or clomiphene citrate (CC) the most effective stimulation regimen in terms of ongoing pregnancies in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria as a measure to reduce the number of multiple pregnancies? SUMMARY ANSWER: In IUI with adherence to strict cancellation criteria, ovarian stimulation with FSH is not superior to CC in terms of the cumulative ongoing pregnancy rate, and yields a similar, low multiple pregnancy rate. WHAT IS ALREADY KNOWN: FSH has been shown to result in higher pregnancy rates compared to CC, but at the cost of high multiple pregnancy rates. To reduce the risk of multiple pregnancy, new ovarian stimulation regimens have been suggested, these include strict cancellation criteria to limit the number of dominant follicles per cycle i.e. withholding insemination when more than three dominant follicles develop. With such a strategy, it is unclear whether the ovarian stimulation should be done with FSH or with CC. STUDY DESIGN, SIZE, DURATION: We performed an open-label multicenter randomized superiority controlled trial in the Netherlands (NTR 4057). PARTICIPANTS/MATERIALS, SETTING, METHODS: We randomized couples diagnosed with unexplained subfertility and scheduled for a maximum of four cycles of IUI with ovarian stimulation with 75 IU FSH or 100 mg CC. Cycles were cancelled when more then three dominant follicles developed. The primary outcome was cumulative ongoing pregnancy rate. Multiple pregnancy was a secondary outcome. We analysed the data on intention to treat basis. We calculated relative risks and absolute risk difference with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: Between July 2013 and March 2016, we allocated 369 women to ovarian stimulation with FSH and 369 women to ovarian stimulation with CC. A total of 113 women (31%) had an ongoing pregnancy following ovarian stimulation with FSH and 97 women (26%) had an ongoing pregnancy following ovarian stimulation with CC (RR = 1.16, 95% CI: 0.93-1.47, ARD = 0.04, 95% CI: -0.02 to 0.11). Five women (1.4%) had a multiple pregnancy following ovarian stimulation with FSH and eight women (2.2%) had a multiple pregnancy following ovarian stimulation with CC (RR = 0.63, 95% CI: 0.21-1.89, ARD = -0.01, 95% CI: -0.03 to 0.01). LIMITATIONS, REASONS FOR CAUTION: We were not able to blind this study due to the nature of the interventions. We consider it unlikely that this has introduced performance bias, since pregnancy outcomes are objective outcome measures. WIDER IMPLICATIONS OF THE FINDINGS: We revealed that adherence to strict cancellation criteria is a successful solution to reduce the number of multiple pregnancies in IUI. To decide whether ovarian stimulation with FSH or with CC should be the regimen of choice, costs and patients' preferences should be taken into account.
引用
收藏
页码:1866 / 1874
页数:9
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