Extended regime of letrozole in IUI cycle

 

.Extended Letrozole therapy in IUI cycle with incremental dose? Below are the  reference on “Extended dose of letrozole in Unexplained subfertility when IUI is planned” . 

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

Usama M Fouda¹ and Ahmed M Sayed¹

 Disclaimer135532

PMID: 21693030

 

 

Background

The aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and intrauterine insemination (IUI).

Methods

Two hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine insemination was performed 36 to 40 hours after HCG administration.

Results

Both groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively).

Conclusion

The extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI.

Trial registration

ClinicalTrials.gov, NCT01232075

Unexplained infertility is one of the most frequent infertility diagnoses encountered by the gynecologists. Various studies reported that 10 to 30% of infertile couples have unexplained infertility .Superovulation and intrauterine insemination (IUI) is an effective treatment for women with unexplained infertility.

Superovulation increases the probability of pregnancy by increasing the number of oocytes suitable for fertilization or by correcting any subtle defect in ovulation. Furthermore, IUI increases the concentration of active motile sperms reaching the fallopian tubes and overcomes male factors or cervical factors of infertility not detected by conventional infertility tests.

 

 

Earlier Clomiphene used to prescribe for this purpose.  Now it is evident that letrozole can be used as an alternative to clomiphene citrate for superovulation in patients with unexplained infertility.

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 .

DOSE  :  Coming to the  optimal dose and duration of letrozole administration for superovulation in patients with unexplained infertility are still not clear. In various studies reporting the use of letrozole for superovulation, letrozole Dose 1:  was administered from cycle 3 to 7 with daily dose ranging from 2.5 mg to 7.5 mg .

In a randomized controlled trial, Al-Fadhli et al found that the pregnancy rate was significantly higher in patients with unexplained infertility Dose 2 :  treated with 5 mg/day compared with those treated with 2.5 mg/day .

Dose 3 : 7.5 mg OD :  On the other hand, a recent randomized controlled trial revealed that the pregnancy rates were comparable in three groups of patients with unexplained infertility treated with. three different doses of letrozole (2.5, 5 or 7.5 mg/day.

HOW LONG TO ADMINISTER  ??  In a recent study, Badawy et al reported that the extended letrozole regimen (2.5 mg/day from cycle day 1 to 10) resulted in higher pregnancy rate compared with short high dose letrozole regimen (5 mg/day for 5 days) in clomiphene-resistant women with polycystic ovary syndrome (Badawy A, Metwally M, Fawzy M. Randomized controlled trial of three doses of letrozole for ovulation induction in patients with unexplained infertility. Reprod Biomed Online. 2007;14(5):559–562. doi: 10.1016/S1472-6483(10)61046-2. [PubMed] [CrossRef] [Google Scholar])

The aim of this current randomized controlled trial was to compare the efficacy of extended letrozole regimen (2.5 mg/day from cycle day 1 to 9) with clomiphene citrate (100 mg/day from cycle day 3 to 7) in women with unexplained subfertility undergoing superovulation and IUI.

Take home message from this study:  The data presented in our study indicated that the extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation combined with IUI.

 

 

 

For more than four decades, clomiphene citrate has been the first line therapy for induction of ovulation in women with anovulatory infertility and for superovulation in couples with unexplained infertility, mild endometriosis and mild male factor of infertility.

Clomiphene citrate is cheap, orally administered and is associated with very low risk of high-order multiple gestation and severe ovarian hyperstimulation syndrome (OHSS).. However, clomiphene citrate induces prolonged estrogen receptors depletion and therefore exerts antiestrogenic effect on estrogen target tissues as endocervix and endometrium. Several studies revealed that clomiphene citrate has a deleterious effect on cervical mucus quantity and quality and endometrial development resulting in decreased uterine blood flow, endometrial thinning, luteal phase defect and implantation failure .

During the past decade, letrozole (aromatase inhibitor approved by FDA for the treatment of postmenopausal women with breast cancer) has been successfully used for induction of ovulation in anovulatory patients with polycystic ovary syndrome (PCOS) and for augmentation of ovulation in ovulatory women . In contrast to clomiphene citrate, letrozole is rapidly eliminated from the body and does not deplete estrogen receptors and therefore has no adverse effect on endometrium or endocervix .