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. 2025 Jul 26;17(7):e88802.
doi: 10.7759/cureus.88802. eCollection 2025 Jul.

Comparison of Letrozole Versus Clomiphene Citrate Combined With Human Menopausal Gonadotropin in Women With Clomiphene-Resistant Anovulatory Infertility Undergoing Intrauterine Insemination: A Retrospective Cohort Study

Tithi Barman  1 , Vinita Singh  1 , Nilajkumar D Bagde  1
Affiliations

Comparison of Letrozole Versus Clomiphene Citrate Combined With Human Menopausal Gonadotropin in Women With Clomiphene-Resistant Anovulatory Infertility Undergoing Intrauterine Insemination: A Retrospective Cohort Study

Tithi Barman et al. Cureus. .

Abstract

Background Millions of people of reproductive age worldwide struggle with infertility. Treatments such as controlled ovarian hyperstimulation and intrauterine insemination (IUI) are commonly used to address various causes of infertility. Medications such as clomiphene citrate (CC) and letrozole, when combined with human menopausal gonadotropin (HMG), have been shown to improve pregnancy rates and reduce treatment costs. Objective This study aimed to compare the effect of minimal stimulation using HMG with either CC or letrozole for ovulation induction in women with CC-resistant anovulatory infertility. It also assessed the impact of these combinations on follicular development and endometrial thickness. Materials and methods This retrospective cohort study included data from 84 infertile women diagnosed with polycystic ovary syndrome (PCOS). Participant records were retrieved from the hospital database at AIIMS, Raipur, India, covering the period from April 2021 to August 2022. Women were divided into two groups based on their treatment: one group received CC 100 mg and the other letrozole 5 mg, both in combination with HMG administered on alternate days. Forty-two women received letrozole + HMG and 40 received CC + HMG. Two participants in the CC group were excluded due to the development of four dominant follicles. Transvaginal ultrasound was performed on alternate days until follicles exceeded 17 mm. IUI was carried out 36 hours after HCG administration. Fourteen days later, a urinary pregnancy test was done if the participant had not yet menstruated. The clinical pregnancy rates were compared between the two groups. Results There was no significant difference between the two groups in terms of mean follicular diameter, number of dominant follicles, endometrial thickness, HMG dosage required, or the number of days to achieve dominant follicle formation. The IUI outcomes were also comparable in both groups. Conclusion The study concludes that both letrozole and CC, when combined with HMGs, are equally effective in inducing ovulation and achieving successful IUI outcomes in women with CC-resistant anovulatory infertility.

Keywords: clomiphene citrate; human menopausal gonadotropin; infertility; intrauterine insemination; letrozole; ovulation induction.

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Conflict of interest statement

Human subjects: Informed consent for treatment and open access publication was obtained or waived by all participants in this study. Institute Ethics Committee, All India Institute of Medical Sciences, Raipur issued approval 2061/IEC-AIIMSRPR/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Duration of infertility and IUI outcomes in the letrozole + HMG group
The Mann-Whitney U test was used. The duration of infertility was measured in years. p = 0.056. IUI: intrauterine insemination, HMG: human menopausal gonadotropin.
Figure 2
Figure 2. Duration of infertility and IUI outcomes in the CC + HMG group
The Mann-Whitney U test was used. The duration of infertility was measured in years. p = 0.631. IUI: intrauterine insemination, CC: clomiphene citrate, HMG: human menopausal gonadotropin.
Figure 3
Figure 3. Day 2 AFC and IUI outcomes in the letrozole + HMG group
The Mann-Whitney U test was used. p < 0.05 is considered statistically significant. AFC: antral follicle count, IUI: intrauterine insemination, HMG: human menopausal gonadotropin.
Figure 4
Figure 4. Day 2 AFC and IUI outcomes in the CC + HMG group
The Mann-Whitney U test was used. p < 0.05 is considered statistically significant. AFC: antral follicle count, IUI: intrauterine insemination, CC: clomiphene citrate, HMG: human menopausal gonadotropin.
Figure 5
Figure 5. Number of dominant follicles and IUI outcomes in the letrozole + HMG group
The Mann-Whitney U test was used. p < 0.05 is considered statistically significant. HMG: human menopausal gonadotropin.
Figure 6
Figure 6. Number of dominant follicles and IUI outcomes in the CC + HMG group
The Mann-Whitney U test was used. p < 0.05 is considered statistically significant. IUI: intrauterine insemination, CC: clomiphene citrate, HMG: human menopausal gonadotropin.
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