Cited by 132Reproductive Health and TechnologiesOvarian function and disordersReproductive Biology and Fertility

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Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination

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Abstract

Objective To investigate the effects of letrozole in patients undergoing superovulation with gonadotropins and IUI.Design Retrospective analysis.Setting Academic teaching hospital.Patient(s) Women younger than 40 years of age with patent fallopian tubes and infertility of more than 1 year in duration who were undergoing IUI and gonadotropin therapy.Intervention(s) Gonadotropins alone administered from day 3 or a combination of letrozole, 5 mg/d on day 3 to 7, and gonadotropins starting on day 5 of the menstrual cycle. Ultrasonography was performed before initiation of treatment, on day 9 of menstrual cycle, and as required thereafter until the dominant follicle reached 18 mm in diameter. Ovulation was triggered with 10,000 IU of hCG, and IUI was performed 24 and 48 hours later.Main outcome measure(s) Gonadotropin requirements, endometrial thickness, number of follicles, and pregnancy rate.Result(s) All 205 IUI treatment cycles conducted from March 2001 to March 2002 were included. Gonadotropins alone were used in 145 cycles and combination therapy was used in 60 cycles. Patients cotreated with letrozole required fewer gonadotropin administrations (median difference, 300 IU [95% confidence interval (CI), 225-375 IU]), developed more follicles larger than 14 mm (median difference, 1 follicle [95% CI, 1-2 follicles), and had a thinner endometrium (median difference, 1 mm [95% CI, 0.4-1.6 mm]). The pregnancy rate did not differ between patients using gonadotropin alone and those using gonadotropin plus letrozole (20.9% vs. 21.6%).Conclusion(s) The addition of letrozole to gonadotropins decreases gonadotropin requirements, increases the number of pre-ovulatory follicles and decreases endometrial thickness, without a negative effect on pregnancy rates.

Overview

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TL;DR

In this retrospective analysis of 205 IUI cycles, adding letrozole to gonadotropins reduced gonadotropin requirements and increased preovulatory follicles but decreased endometrial thickness, without changing pregnancy rate. The authors conclude that prospective randomized trials are needed to clarify letrozole’s role as a cotreatment in superovulation and IUI.

Key findings

  • Letrozole plus gonadotropins required less gonadotropin to reach follicular maturity than gonadotropins alone (mean 600.6 ± 405.7 IU vs. 940.6 ± 464.2 IU; P<.0001; median difference, 300 IU [95% CI, 225–375 IU]) and fewer days (7.6 ± 2.0 vs. 9.5 ± 3.0; P<.0001; median difference, −2 days [95% CI, −2 to 1 days]).
  • Letrozole cotreatment produced more follicles: follicles >14 mm at hCG administration (3.2 ± 1.2 vs. 2.2 ± 1.5; P<.001; median difference, 1 follicle [95% CI, 1–2]) and follicles >8 mm (5.7 ± 2.7 vs. 4.9 ± 4.3; P=.0008).
  • Endometrial thickness at hCG administration was thinner with letrozole (8.5 ± 2.6 mm vs. 9.4 ± 1.9 mm; P<.001; median difference, 1 mm [95% CI, 0.4–1.6 mm]).
  • Pregnancy rate per cycle started did not differ between groups (21.6% vs. 20.9%; NS in Table 1); no multiple pregnancies occurred in the letrozole plus gonadotropin group, whereas three twin pregnancies occurred in the gonadotropin-alone group.

Methods

  • Retrospective analysis at an academic teaching hospital, March 2001–March 2002; 107 patients and 205 IUI cycles were included, with 145 cycles using gonadotropins alone and 60 using letrozole plus gonadotropins. Inclusion criteria were age younger than 40 years, infertility >1 year, patent fallopian tubes, normal uterine cavity, and at least 10 million rapidly motile sperm/mL.
  • Gonadotropins alone began on day 3, or letrozole 5 mg/d was given on days 3–7 plus gonadotropins starting on day 5; the starting gonadotropin dose was 150 IU every 2 days and was modified as needed. hCG 10,000 IU was given when at least one follicle reached 18 mm, and IUI was performed 24 and 48 hours later.
  • Data were tested for normality with the Shapiro-Wilks test; because data were not normally distributed, Mann-Whitney tests were used, with chi-square and Fisher exact tests for proportions and 95% CIs reported; P<.05 was considered statistically significant.

Limitations

  • The authors state the study is limited by its retrospective nature and that treatment choice was based on physician preference, so some bias may have been introduced; they note the groups were similar in age, indications, and treatment history, and that two technicians performed all ultrasonographic scans and the same embryologist prepared IUI samples.
  • The authors note the anovulatory subgroup comprised only patients with PCOS, and not all underwent testing or treatment for insulin resistance, which may account for differences in ovarian sensitivity to gonadotropins.
  • Evident in the text: the pregnancy-rate result is internally inconsistent—the paper states no difference and Table 1 marks pregnancy rate NS, but also reports an odds ratio of 1.8 (95% CI, 1.1–3.2); the letrozole plus gonadotropin group was also much smaller (60 cycles) than the gonadotropin-alone group (145 cycles).

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Integrity signals

Registry

Crossref · 10.1016/j.fertnstert.2003.03.001

Cites

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Citations

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  1. Buzdar, 2001, Howell A. Advances in aromatase inhibition, Clin Cancer Res, 7, 2620

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Metadata

Authors
Healey, S., Tan, S. L., Tulandi, T., & Biljan, M. M.
Affiliations
McGill University (CA)
Corresponding author
Healey, Sarah
Venue
Fertility and Sterility
Publisher
Elsevier BV
Published
2003-12
Volume
80
Issue
6
Pages
1325-1329
ISSN
0015-0282 (ISSN-L)
OpenAlex
W2158299014
Cited by
132
References
36
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2022: 8 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 7
FWCI
10.42
Type
journal article
Language
en
Open access
Locations
  • Fertility and Sterility (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
Keywords
letrozole, superovulation, gonadotropins, intrauterine insemination, infertility, endometrial thickness, follicle count, pregnancy rate, ovulation induction, hCG trigger
MeSH terms
Letrozole, Adult, Enzyme Inhibitors, Female, Chorionic Gonadotropin, Hospitals, Teaching, Humans, Insemination, Artificial, Nitriles, Pregnancy, Pregnancy Outcome, Retrospective Studies, Superovulation, Triazoles, Aromatase Inhibitors

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