Minimal Stimulation Using Gonadotropin Combined with Clomiphene Citrate or Letrozole for Intrauterine Insemination

다국어 초록 (Multilingual Abstract)

Purpose: To evaluate the efficacy of minimal stimulation using discretely administeredgonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. Materials and Methods: Total 257 IUI cyclesfrom 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3‒5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropinat a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combinedwith alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). Results: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarianhyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). Conclusion: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiplepregnancies, while maintaining comparable pregnancy rates in IUI cycles.

참고문헌 (Reference)

• 1 Hughes EG, "The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility: a meta-analysis" 12 : 1865-1872, 1997
• 2 Zegers-Hochschild F, "The International Committee Monitoring Assisted Reproductive Technologies (ICMART) glossary on ART terminology" 86 : 16-19, 2006
• 3 Zegers-Hochschild F, "The ICMART glossary on ART terminology" 21 : 1968-1970, 2006
• 4 Stewart JA, "Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. Should the guidelines be changed?" 18 : 903-907, 2003
• 5 Dickey RP, "Sequential clomiphene citrate and human menopausal gonadotrophin for ovulation induction: comparison to clomiphene citrate alone and human menopausal gonadotrophin alone" 8 : 56-59, 1993
• 6 Dickey RP, "Risk factors for high-order multiple pregnancy and multiple birth after controlled ovarian hyperstimulation: results of 4,062 intrauterine insemination cycles" 83 : 671-683, 2005
• 7 Tur R, "Risk factors for high-order multiple implantation after ovarian stimulation with gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a single centre" 16 : 2124-2129, 2001
• 8 Ghesquiere SL, "Relationship between follicle number and (multiple) live birth rate after controlled ovarian hyperstimulation and intrauterine insemination" 197 : 589-, 2007
• 9 Gleicher N, "Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins" 343 : 2-7, 2000
• 10 Gregoriou O, "Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine insemination" 90 : 678-683, 2008
• 11 Ragni G, "Preventing high-order multiple pregnancies during controlled ovarian hyperstimulation and intrauterine insemination: 3 yearsʼ experience using low-dose recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists" 85 : 619-624, 2006
• 12 Cantineau AE, "Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility" CD005356-, 2007
• 13 Navot D, "Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment" 58 : 249-261, 1992
• 14 Ryan GL, "Oral ovulation induction agents combined with low-dose gonadotropin injections and intrauterine insemination: cost- and clinical effectiveness" 50 : 943-950, 2005
• 15 Ombelet W, "Multiple gestation and infertility treatment: registration, reflection and reaction-- the Belgian project" 11 : 3-14, 2005
• 16 Dhaliwal LK, "Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility" 28 : 295-299, 2002
• 17 Lu PY, "Minimal stimulation achieves pregnancy rates comparable to human menopausal gonadotropins in the treatment of infertility" 65 : 583-587, 1996
• 18 Fauser BC, "Macklon NS. Multiple birth resulting from ovarian stimulation for subfertility treatment" 365 : 1807-1816, 2005
• 19 ESHRE Capri Workshop Group, "Intrauterine insemination" 15 : 265-277, 2009
• 20 Wolff EF, "Influences on endometrial development during intrauterine insemination: clinical experience of 2,929 patients with unexplained infertility" 100 : 194-199, 2013
• 21 Bhattacharya S, "In treating infertility, are multiple pregnancies unavoidable?" 343 : 58-60, 2000
• 22 Goverde AJ, "Further considerations on natural or mild hyperstimulation cycles for intrauterine insemination treatment : effects on pregnancy and multiple pregnancy rates" 20 : 3141-3146, 2005
• 23 Brzechffa PR, "Female and male partner age and menotrophin requirements influence pregnancy rates with human menopausal gonadotrophin therapy in combination with intrauterine insemination" 12 : 29-33, 1997
• 24 Guzick DS, "Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network" 340 : 177-183, 1999
• 25 Healey S, "Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination" 80 : 1325-1329, 2003
• 26 Bedaiwy MA, "Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation" 21 : 2838-2844, 2006
• 27 Barroso G, "Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant follicle-stimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial" 86 : 1428-1431, 2006
• 28 Ganesh A, "Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure : a randomized prospective clinical trial" 26 : 19-24, 2009
• 29 Agarwal SK, "Clomiphene citrate with intrauterine in semination: is it effective therapy in women above the age of 35 years?" 65 : 759-763, 1996
• 30 Badawy A, "Clomiphene citrate or aromatase inhibitors combined with gonadotropins for superovulation in women undergoing intrauterine insemination: a prospective randomised trial" 30 : 617-621, 2010
• 31 McKnight KK, "Body mass index-associated differences in response to ovulation induction with letrozole" 96 : 1206-1208, 2011
• 32 Franik S, "Aromatase inhibitors for subfertile women with polycystic ovary syndrome" 2 : CD010287-, 2014
• 33 Lee VC, "Aromatase inhibitors for ovulation induction and ovarian stimulation" 74 : 537-546, 2011
• 34 Sengoku K, "A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility" 9 : 1043-1047, 1994
• 35 Sagnella F, "A prospective randomized noninferiority study comparing recombinant FSH and highly purified menotropin in intrauterine insemination cycles in couples with unexplained infertility and/or mild-moderate male factor" 95 : 689-694, 2011