Treatment of Unexplained Infertility With Aromatase Inhibitors or Clomiphene Citrate

Abstract

Treatment of unexplained infertility is empiric and different regimens or protocols have been used so far. Clomiphene can be used alone or combined with gonadotrophins. Aromatase inhibitors may offer an alternative for first-line treatment. To compare the efficacy of aromatase inhibitors versus climiphene, we conducted a systematic review and meta-analysis for randomized controlled trials comparing the above regimens to estimate live pregnancy rates in women with unexplained infertility. Trials were located through PubMed and Cochrane Library searches. Methodological quality of included trials has been assessed. Then, 2 x 2 tables were constructed, and pooled odds ratios (ORs) were calculated. Ten arms (273 patients) were included in the meta-analysis. ORs were homogeneous between studies (heterogeneity chi2 = 2.33, P = 0.676). No difference was observed for live pregnancies (pooled OR 0.87, 95% CI, 0.46-1.65, P = 0.666) for aromatase inhibitors versus clomiphene citrate; however, the definition of live pregnancy by the authors was clear only in one trial. Data regarding secondary outcomes were omitted, and methodogical quality of eligible trials did not reach high scores. Evidence from randomized data regarding the use of aromatase inhibitors is fragmented and weak. Aromatase inhibitors may have a role in the treatment of women with unexplained infertility desiring pregnancy. However, meticulous reporting and study design should be a priority in this field and large, registered, and properly designed randomized trials are essential to test whether aromatase inhibitors can be introduced as a first-line treatment in carefully selected subgroups of women with unexplained infertility.

Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

“…The majority of studies comparing clomiphene citrate with letrozole for superovulation in patients with unexplained infertility undergoing IUI revealed that although letrozole induced fewer mature follicles compared with clomiphene citrate the pregnancy rate was comparable between both management options[9,12]. We think that letrozole resulted in comparable pregnancy rate as clomiphene citrate, in spite of less number of mature oocytes induced, because it has no adverse effect on endometrium.…”

“…Several studies revealed that the combination of exogenous gonadotropins with letrozole increased the number of mature oocytes and therefore improved the outcome of IUI cycles in patients with unexplained infertility [6,12]. However, the addition of exogenous gonadotropins to letrozole increases the cost of IUI cycle and is associated with increased risk of higher order multiple pregnancy and ovarian hyperstimulation syndrome.…”

“…Several studies revealed that letrozole can be used as an alternative to clomiphene citrate for superovulation in patients with unexplained infertility [12,13]. A meta-analysis of seven randomized controlled trials comparing aromatase inhibitors (letrozole or anastrozole) with clomiphene citrate for superovulation in patients with unexplained infertility undergoing IUI revealed that the pregnancy rate was comparable between both management options [14].…”

Definitions and Epidemiology of Unexplained Female Infertility

“…The differences in diagnostic methods to evaluate the infertile couples and variable means of data collection make them very inhomogeneous. Women suffering from unexplained subfertility have both delayed and decreased fecundity with an average cycle fecundity reported between 2 and 4 % per menstrual cycle [32,33].…”

Role of In Vitro Fertilization in Unexplained Female Infertility

“…These include ovulation induction with clomiphene citrate (CC) [8], gonadotrophins (HMG) [9], or aromatase inhibitors [10], flushing the uterine cavity with various physiological solutions or radio-opaque medium [11], empirical use of bromocryptin [12] or danazol [13], intrauterine insemination (IUI) with or without controlled ovarian hyperstimulation (COH) [14][15][16][17][18], intraperitoneal insemination (IPI) [19], fallopian tube sperm perfusion [20], gamete intrafallopian transfer (GIFT), as well as in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) [16,[21][22][23]. This chapter will evaluate the role of IVF in unexplained female infertility in the light of evidence.…”